A role for adenosine A2 receptors in the induction of long-term potentiation in the CA1 region of rat hippocampus.
A role for adenosine A2 receptors in the induction of long-term potentiation in the CA1 region of rat hippocampus.
复制标题
腺苷 A2 受体在诱导大鼠海马 CA1 区长时程增强中的作用。
DOI：
10.1016/s0006-8993(97)00148-0
复制
发表时间：
1997
期刊：
影响因子：
2.9
通讯作者：
Mogul,DJ
中科院分区：
文献类型：
--
作者：
Kessey,K;Trommer,BL;Overstreet,LS;Ji,T;Mogul,DJ
尽管有报道称激动剂介导的腺苷A1受体激活会导致神经传递减少，但A2受体激活对突触传递的影响尚未得到很好的研究。我们研究了腺苷A2受体在大鼠横向海马脑片中Schaffer侧支-CA1通路之间的神经传递功效中的作用。在完全抑制A1受体的情况下，A2受体阻断导致对低频测试脉冲（0.033 Hz）的场兴奋性突触后电位（EPSP）斜率的可逆性降低，表明A2受体可以增强突触传递。用A2受体拮抗剂DMPX（3，7-dimethyl-1-propargylxanthine）阻断A2受体可阻断破伤风诱发的EPSP长时程增强（LTP）。相反，在A1受体阻断过程中没有观察到对LTP诱导的这种影响。我们还研究了在用CPT持续阻断A1受体期间DMPX对LTP诱导的影响。在这种情况下，LTP显着降低时，与LTP诱导的CPT单独存在。用高极性的A2受体拮抗剂8-SPT（8-（p-sulfophenyl）theophylline）也得到类似的结果，提示DMPX对LTP的影响不是直接作用于细胞内的中间产物。在破伤风后45分钟应用DMPX对LTP表达没有影响，表明A2受体在LTP的维持期没有显著作用。选择性A2a受体激活不改变EPSP场。同样，选择性阻断A2a受体也不干扰破伤风诱导的LTP。神经元放电率的增加可导致细胞外腺苷浓度的升高。总之，这些结果表明，A2受体可能在诱导海马LTP中发挥重要作用，但不是维持海马LTP，并且这种作用可能是由A2b受体介导的。
Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1receptor activation, the implications of A2receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A2receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A2receptor blockade in the presence of complete A1receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A2receptors can enhance synaptic transmission. A2receptor blockade by the A2antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A1receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A1receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A2antagonist 8-SPT (8-(p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A2receptors play no significant role in the maintenance phase of LTP. Selective A2areceptor activation did not alter the field EPSP. Similarly, selective blockade of the A2areceptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A2receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A2breceptor.